This sections discusses the definition of a bio-artificial pancreas, difficulties leading to their usual failure, our design objectives, and the qualities of the Islet Sheet.

Definition

The bio-artificial pancreas is fabricated from living and nonliving components. The living component is islets of Langerhans, which sense glucose and secrete insulin. The nonliving component protects the islets from the diabetic's body yet permits the islets inside to thrive.

A bio-artificial endocrine pancreas replaces nonfunctioning islets of Langerhans. It responds to changing blood composition with release of hormones including insulin. A bio-artificial pancreas is implanted into the peritoneal cavity of the diabetic and contains two to three million cells.

Bio-artificial pancreas designs come in four physical types: hollow fibers, capsules, coatings and sheets. As we will see in the next section only coatings or thin sheets have dimensions capable of permitting the islets inside to function normally.

To the right is a micrograph of the most successful thin coating, developed by Randy Dorian and researchers at the University of California. (Click on the photo to see a larger version.)

Problems with the Bio-Artificial Pancreas

We believe that the bio-artificial pancreas is the most promising potential cure for diabetes. But technical requirements for a bio-artificial pancreas are exacting and have proven very difficult to solve.

Why has the problem proven intractable? Because the islets inside most bio-artificial pancreases die of starvation. Most often the surface of the bio-artificial pancreas provokes a foreign body response; the resulting fibrotic reaction walls off the device and the islets cannot get nutrition. Another problem has been that the dimensions of most bio-artificial pancreases do not permit oxygen to penetrate to the core of the device. Sometimes the process used to make the device damages or destroys the islets.

Design Objectives for Bio-Artificial Pancreas

We set out to make the perfect bio-artificial pancreas, and determined the following as the essential design objectives shown in the figure.

Click on each design objective to learn more.

  1. Keeps the islets alive and functioning
    1. material contacting islets must be biocompatible
    2. process for fabrication must not damage islets
    3. dimensions must permit rapid diffusion of nutrients
    4. dimensions must permit rapid diffusion of insulin
  2. Prevent destructive host response
    1. outer surfaces must be totally biocompatible (provoking no fibrotic response)
    2. all islets must be completely covered (to prevent immune sensitization)
    3. permeability must be controllable
  3. Assure practical surgical implantation
    1. islet density must be high (sheet size is not too large)
    2. must be retrievable
    3. must be bio-stable
    4. must be chemically durable
    5. must by physically durable
    6. must be surgically acceptable

The Islet Sheet

In the Islet Sheet, islets are kept alive by diffusion of oxygen, glucose and other nutrients into the sheet; insulin, hormones and waste products diffuse out of the sheet. The sheet is so thin that diffusion alone allows sufficient nutrients to reach the center of the sheet. A coat on the exterior of the sheet prevents contact between the cells inside and immune effector cells of the host as well as inhibiting diffusion of antibody and complement. No immune suppression drugs are needed. The sheet may be removed or replaced at any time.

This figure shows an electron micrograph of an Islet Sheet.